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Biomedical subjects

Hui Fang

Publications and source records attributed to Hui Fang.

At least 19 recordsLinked to original sources

Metal-particle-induced, highly localized site-specific etching of Si and formation of single-crystalline Si nanowires in aqueous fluoride solution.

A straightforward metal-particle-induced, highly localized site-specific corrosion-like mechanism was proposed for the formation of aligned silicon-nanowire arrays on silicon in aqueous HF/AgNO3 solution on the basis of convincing experimental results. The etching process features weak dependence on the doping of the silicon wafers and, thus, provides an efficient method to prepare silicon nanowires with desirable doping characteristics. The novel electrochemical properties between silicon and active noble metals should be useful for preparing novel silicon nanostructures and also new optoelectronic devices.

Journal Article↗

Edge effect in fluid jet polishing.

The edge effect is one of the most important subjects in optical manufacturing. The removal function at different positions of the sample in the process of fluid jet polishing (FJP) is investigated in the experiments. Furthermore, by using finite-element analysis (FEA), the distributions for velocity and pressure of slurry jets are simulated. Experimental results demonstrate that the removal function has a ring-shaped profile, except for a little change in the size at the operated area even if the nozzle extends beyond the edge of the sample. FEA simulations reveal a similar distribution of velocity with a cavity resulting in the ring-shaped profile of material removal at different impact positions. To a certain extent, therefore, the removal function at the edge of the surface of the sample appears similar to that inside of it, so that the classical edge effect can be neglected in FJP.

Journal Article↗

Dwell function algorithm in fluid jet polishing.

Considering the special characteristics of the removal function with the ring-shaped profile in fluid jet polishing (FJP), we present an effective method called the discrete convolution algorithm to compute the dwell function for controlling the figuring process. This method avoids the deconvolution operation, which usually fails to converge. Then an experimental confirmation of FJP figuring was demonstrated by machining a one-dimensional depth profile on a flat sample. The profile was figured from 0.914lambda(lambda=632.8 nm) peak to valley (PV) to 0.260lambda. This experiment demonstrated the successful implementation of the algorithm to solve the dwell function in optical manufacturing.

Journal Article↗

Surface roughness and material removal in fluid jet polishing.

Based on experiments, the dependence of material removal and surface roughness on the characteristics of abrasive particles, on the workpiece, and on other process parameters such as working pressure and incidence angle in fluid jet polishing (FJP) technology were investigated. Experimental results show a volume removal rate that is approximately proportional to the square root of the Young's modulus (E) and inversely proportional to the square of the Knoop hardness (Hk) of glass. Similarly, surface roughness is also determined in FJP by elastic stiffness E and plastic parameter Hk. The influence of the incidence angle on surface roughness and material removal were studied, and a linear dependence of material removal on the working pressure was obtained. Further, it was found that an optical-quality surface can be achieved by use of Cerox 1650 abrasive particles in FJP and can satisfy the requirements of modern optical manufacturing.

Journal Article↗

Anthrax lethal toxin has direct and potent inhibitory effects on B cell proliferation and immunoglobulin production.

Protective host immune responses to anthrax infection in humans and animal models are characterized by the development of neutralizing Abs against the receptor-binding anthrax protective Ag (PA), which, together with the lethal factor (LF) protease, composes anthrax lethal toxin (LT). We now report that B cells, in turn, are targets for LT. Anthrax PA directly binds primary B cells, resulting in the LF-dependent cleavage of the MAPK kinases (MAPKKs) and disrupted signaling to downstream MAPK targets. Although not directly lethal to B cells, anthrax LT treatment causes severe B cell dysfunction, greatly reducing proliferative responses to IL-4-, anti-IgM-, and/or anti-CD40 stimulation. Moreover, B cells treated with anthrax LT in vitro or isolated from mice treated with anthrax LT in vivo have a markedly diminished capacity to proliferate and produce IgM in response to TLR-2 and TLR-4 ligands. The suppressive effects of anthrax LT on B cell function occur at picomolar concentrations in vitro and at sublethal doses in vivo. These results indicate that anthrax LT directly inhibits the function of B cells in vitro and in vivo, revealing a potential mechanism through which the pathogen could bypass protective immune responses.

Animals↗

Capillary-based, serial-loading, parallel microreactor for catalyst screening.

Soluble metal-ligand complexes are useful as catalysts for many organic reactions. The large number of metals and ligands available suggests a combinatorial approach to catalyst discovery. Carrying out reactions in very small (microliter) volumes in capillaries has many advantages in this regard, including material conservation, isolation from the atmosphere, and ease of transport of species by using pressure-induced flow. We have developed a capillary reactor in which separate zones of catalyst and reactants are combined and react. Zones are loaded serially into the capillary reactor from an autosampler, they react in parallel in the capillary reactor (at elevated temperature) and are ejected serially and under computer control for analysis by online GC. Offline analysis following sample collection is also possible. The Stille cross-coupling reaction has been the focus of our recent activity. Known palladium-based precatalysts and phosphine or arsine ligands were screened to validate the approach taken here. The results largely agree with results obtained by traditional organic synthesis, validating the method. The throughput of the nonoptimized system is over two 5-h reactions/h. For example, 40 5-h reactions examining the effect of catalyst loading were performed in 2 9-h runs requiring a total of 2 h of operator time.

Arsenicals↗

[Prognostic factors of primary non-Hodgkin's lymphoma of the nasal cavity--a report of 129 cases].

BACKGROUND & OBJECTIVE: The prognosis of primary non-Hodgkin's lymphoma (NHL) of the nasal cavity was poor, and the distant metastasis and local relapse rates are high. This study was to analyze the prognostic factors of this disease. METHODS: Clinical data of 129 patients with pathologically confirmed nasal NHL, treated from Jan. 1996 to Dec. 2002, were retrospectively reviewed. Of the 129 patients, 116 were diagnosed as nasal NK/T-cell lymphoma. According to the Ann Arbor staging system, 102 patients had stage IE disease, 22 stage IIE, and 5 stage IVE. Among the 124 patients with stage IE or IIE disease, 22 received radiotherapy alone, 7 received chemotherapy alone, and 95 received combined modality therapy (CMT). Of the patients received CMT, 45 received radiotherapy followed by chemotherapy, and 50 received chemotherapy followed by radiotherapy. The stage IVE patients received chemotherapy with or without radiotherapy. RESULTS: The 5-year overall survival (OS) and disease-freely survival (DFS) rates for all patients were 68.0% and 55.8%, respectively. The 5-year OS and DFS rates were 71.7% and 60.9% for stage IE patients, and 70.6% and 47.0% for stage IIE patients, respectively (P>0.05). The 5-year OS and DFS rates were significantly higher in the patients who achieved complete response (CR) than in those who didn't (83.1% vs. 18.0%, 68.0% vs. 15.5%, P<0.01). The 5-year OS rates of the patients with international prognostic index (IPI) score of 0, 1, and > or =2 were 81.1%, 60.1%, and 14.3% (P<0.01), respectively; the 5-year DFS rates were 68.8%, 44.6%, and 22.5% (P<0.01), respectively. Thirty-eight patients developed progression or relapse, with distant extranodal dissemination (78.9%) as the primary pattern of failure. Univariate analysis showed that CR rate, PS, IPI, and modified IPI were related to prognosis. Multivariate analysis showed that CR rate was an independent prognostic factor. CONCLUSIONS: CR rate after treatment is an important prognostic factor of nasal NHL. Distant metastasis is the main failure pattern of nasal NHL.

Adolescent↗

[Prognostic factors and treatment outcome in early stage nasal NK/T cell lymphoma].

OBJECTIVE: To analyze initial response rate of radiotherapy and chemotherapy for early nasal NK/T-cell lymphoma, and its prognostic factors. METHODS: From January 1996 to December 2002, 116 patients with nasal NK/T-cell lymphoma were diagnosed pathologically. Immunophenotyping was performed in 50 cases. According to Ann Arbor staging classification, 95 patients were stage I(E) and 21 II(E). Of the 116 patients, 22 received radiotherapy alone, 6 chemotherapy alone and 88 combined modality therapy (CMT), including, 41 radiotherapy followed by chemotherapy, and 47 chemotherapy followed by radiotherapy. RESULTS: The 5-year overall survival (OS) rate and disease free survival (DFS) rate for all patients was 74.1% and 61.5%, respectively. For stage I(E) and II(E) patients, the 5-year OS rate was 75.1% and 68% (P = 0.45), and DFS rate was 64.7% and 47.8%, respectively (P = 0.07). The 5 year OS rate and DFS rate were 86.5% and 71.5% for patients who achieved complete response (CR), and 18.4% and 17.2% for those who didn't, respectively (P = 0.000). Sixty-three patients were treated with radiotherapy alone or radiotherapy followed by chemotherapy, while 53 with chemotherapy followed by radiotherapy or chemotherapy alone. The CR rate for radiotherapy was 74.6% while for chemotherapy was 20.8% (P = 0.000). The 5-year OS rate and DFS rate were 76.8% and 65.4% for radiotherapy with or without chemotherapy, and 78.8% and 61.8% for chemotherapy followed by radiotherapy (P > 0.05). Multivariate analysis by COX regression showed that CR rate was the only independent prognostic factor. CONCLUSION: The CR rate of radiotherapy is much higher than that of conventional chemotherapy. Addition of chemotherapy to radiotherapy do not improve the survival of patients with early stage nasal NK/T-cell lymphoma. Radiotherapy is the primary treatment for stage I and II nasal NK/T-cell lymphoma.

Adolescent↗

Variable alternative spliced exon (VASE)-containing and VASE-lacking neural cell adhesion molecule in the dorsal and ventral hippocampus of SAMP8 mice.

The neural cell adhesion molecule (NCAM) is involved in the development and synaptic plasticity of the brain. Differential splicing of the variable alternative spliced exon (VASE) in the fourth immunoglobulin domain can dramatically change the functional properties of NCAM. This paper discusses our analysis of the levels of different expression of VASE-containing NCAM (NCAM-VASE(+)) and VASE-lacking NCAM (NCAM-VASE(-)) mRNAs in the dorsal and ventral hippocampus of senescence-accelerated mice (SAM). We further investigated the individual level of NCAM-VASE(+) and NCAM-VASE(-) in relation to the capacity for spatial learning and memory as assessed by a Morris water maze task. The results showed that the levels of both NCAM-VASE(+) and NCAM-VASE(-) were increased significantly in dorsal but not ventral hippocampus in aged SAMP8 mice. The mean latencies to find the hidden platform of the learning task on the last day were positively correlated with the levels of NCAM-VASE(+) in the dorsal hippocampus of SAMP8, which reveals that the mice with high levels of NCAM-VASE(+) have poor learning performances. These results suggest that the up-regulation of NCAM-VASE(+) could be involved in the impairments of spatial learning and memory.

Aging↗

Anthrax lethal toxin blocks MAPK kinase-dependent IL-2 production in CD4+ T cells.

Anthrax lethal toxin (LT) is a critical virulence factor that cleaves and inactivates MAPK kinases (MAPKKs) in host cells and has been proposed as a therapeutic target in the treatment of human anthrax infections. Despite the potential use of anti-toxin agents in humans, the standard activity assays for anthrax LT are currently based on cytotoxic actions of anthrax LT that are cell-, strain-, and species-specific, which have not been demonstrated to occur in human cells. We now report that T cell proliferation and IL-2 production inversely correlate with anthrax LT levels in human cell assays. The model CD4+ T cell tumor line, Jurkat, is a susceptible target for the specific protease action of anthrax LT. Anthrax LT cleaves and inactivates MAPKKs in Jurkat cells, whereas not affecting proximal or parallel TCR signal transduction pathways. Moreover, anthrax LT specifically inhibits PMA/ionomycin- and anti-CD3-induced IL-2 production in Jurkat cells. An inhibitor of the protease activity of anthrax LT completely restores IL-2 production by anthrax LT-treated Jurkat cells. Anthrax LT acts on primary CD4+ T cells as well, cleaving MAPKKs and leading to a 95% reduction in anti-CD3-induced proliferation and IL-2 production. These findings not only will be useful in the development of new human cell-based bioassays for the activity of anthrax LT, but they also suggest new mechanisms that facilitate immune evasion by Bacillus anthracis. Specifically, anthrax LT inhibits IL-2 production and proliferative responses in CD4+ T cells, thereby blocking functions that are pivotal in the regulation of immune responses.

Antigens, Bacterial↗

[Corresponding analysis on rice grain heavy metal pollution in Fujian province].

By the methods of environmental statistics and corresponding analysis, this paper collected 38 early and late rice grain samples from the middle, southern, northern, western and eastern parts of Fujian Province to detect their Hg, As, Cr, Cd and Pb contents, and to search for the main factors resulting in the difference of rice cropping type in different regions, aiming at further understanding the relationships between heavy metal pollution and rice cropping type. The results showed that among the test heavy metals in grain, Pb had the highest percentage (100%) beyond the standard level, followed by Hg (78.95%), Cd (50.5%) and Cu (2.63%), while As did not surpass the standard level. It therefore could be concluded that Pb and Cd were the main factors resulting in the difference of rice cropping type in different regions. The results also showed that 38 rice grain samples could be clustered into 7 groups, indicating that different rice cropping types would significantly cause different degrees of heavy metal pollution, which suggested that the best way in controlling and preventing rice grain heavy metal pollution could be the approach of combining site-controlling with variety selection, based on the situation of different regions and rice cropping systems.

Cadmium↗

Regulated production of a peroxisome proliferator-activated receptor-gamma ligand during an early phase of adipocyte differentiation in 3T3-L1 adipocytes.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear hormone receptor that is critical for adipogenesis and insulin sensitivity. Ligands for PPARgamma include some polyunsaturated fatty acids and prostanoids and the synthetic high affinity antidiabetic agents thiazolidinediones. However, the identity of a biologically relevant endogenous PPARgamma ligand is unknown, and limited insight exists into the factors that may regulate production of endogenous PPARgamma ligands during adipocyte development. To address this question, we created a line of 3T3-L1 preadipocytes that carry a beta-galactosidase-based PPARgamma ligand-sensing vector system. In this system, induction of adipogenesis resulted in elevated beta-galactosidase activity that signifies activation of PPARgamma via its ligand-binding domain (LBD) and suggests generation and/or accumulation of a ligand moiety. The putative endogenous ligand appeared early in adipogenesis in response to increases in cAMP, accumulated in the medium, and dissipated later in adipogenesis. Organically extracted and high pressure liquid chromatography-fractionated conditioned media from differentiating cells, but not from mature adipocytes, were enriched in this activity. One or more components within the organic extract activated PPARgamma through interaction with its LBD, induced lipid accumulation in 3T3-L1 cells as efficiently as the differentiation mixture, and competed for binding of rosiglitazone to the LBD of PPARgamma. The active species appears to be different from other PPARgamma ligands identified previously. Our findings suggest that a novel biologically relevant PPARgamma ligand is transiently produced in 3T3-L1 cells during adipogenesis.

3T3-L1 Cells↗

Anthrax lethal toxin rapidly activates caspase-1/ICE and induces extracellular release of interleukin (IL)-1beta and IL-18.

Anthrax lethal toxin (LT), a critical virulence factor for Bacillus anthracis, has been demonstrated to cleave and to inactivate mitogen-activated protein kinase kinases (MAPKKs) that propagate prosurvival signals in macrophages (1-5). Whether this action of anthrax LT leads to the production of proinflammatory cytokines by macrophages has been more controversial (6, 7). We now report that anthrax LT treatment leads to the specific extracellular release of interleukin (IL)-1beta and IL-18 by the murine macrophage cell lines, RAW264.7 and J774A.1. Studies of the processing of IL-1beta reveal that the levels of activated/cleaved IL-1beta in RAW264.7 and J774.A1 cells are increased following treatment with anthrax LT. Enhanced processing of IL-1beta directly correlates with increased levels in the activation of its upstream regulator, IL-1beta-converting enzyme/Caspase-1 (ICE). The extracellular release of IL-1beta and IL-18 in response to anthrax LT is ICE-dependent, as an ICE-specific inhibitor blocks this process. These data indicate that ICE, IL-1beta, and IL-18 are downstream effectors of anthrax LT in macrophages, providing the basis for new bioassays for anthrax LT activity and representing potential therapeutic targets.

Animals↗

In vivo studies of endotoxin removal by lysine-cellulose adsorbents.

A new type adsorbent for removal of bacterial endotoxins was prepared by immobilizing lysine covalently onto cellulose beads. Endotoxins (Escherichia coli O55: B5) were injected into 13 healthy New Zealand white rabbits to induce infectious symptoms. Hemoperfusion using the adsorbent column removed endotoxins in the blood of eight rabbits during 2h while other five rabbits were used as control. The mean blood endotoxin concentration was reduced significantly from 5.56 +/- 0.54 EU/ml (1 EU = 100 pg) before treatment to 0.41 +/- 0.26 EU/ml after perfusion as measured by the limulus amebocyte lysate test (Chromogenix). Liver function and renal function tests showed significant improvement of septic symptoms in contrast to the control group. Other parameters such as superoxide dismutase and malondialdehyde were ameliorated markedly after the treatment. Moreover, the adsorbent showed good results in mechanical strength, blood compatibility and cytotoxicity, which suggested that lysine-cellulose adsorbent was of high ET-binding efficacy without significant side effect. It has a high potential of clinical application for treatment of patients with severe sepsis.

Adsorption↗

A study of statistical methods for function prediction of protein motifs.

Automatic discovery of new protein motifs (i.e. amino acid patterns) is one of the major challenges in bioinformatics. Several algorithms have been proposed that can extract statistically significant motif patterns from any set of protein sequences. With these methods, one can generate a large set of candidate motifs that may be biologically meaningful. This article examines methods to predict the functions of these candidate motifs. We use several statistical methods: a popularity method, a mutual information method and probabilistic translation models. These methods capture, from different perspectives, the correlations between the matched motifs of a protein and its assigned Gene Ontology terms that characterise the function of the protein. We evaluate these different methods using the known motifs in the InterPro database. Each method is used to rank candidate terms for each motif. We then use the expected mean reciprocal rank to evaluate the performance. The results show that, in general, all these methods perform well, suggesting that they can all be useful for predicting the function of an unknown motif. Among the methods tested, a probabilistic translation model with a popularity prior performs the best.

Algorithms↗

Glucagon-like peptide-1-responsive catecholamine neurons in the area postrema link peripheral glucagon-like peptide-1 with central autonomic control sites.

Glucagon-like peptide-1 (GLP-1) released from the gut is an incretin that stimulates insulin secretion. GLP-1 is also a brain neuropeptide that has diverse central actions, including inhibition of food and water intake, gastric emptying, and stimulation of neuroendocrine responses characteristic of visceral illness. Both intravenous and intracerebroventricular administration of GLP-1 receptor (GLP-1R) agonists increase blood pressure and heart rate and induce Fos-like immunoreactivity (Fos-IR) in autonomic regulatory sites in the rat brain. The area postrema (AP) is a circumventricular organ and has been implicated in processing visceral sensory information. GLP-1Rs are densely expressed in the AP, and peripheral GLP-1R agonists induce Fos-IR in AP neurons to a greater degree than intracerebroventricular administration. Because the AP lacks a blood-brain barrier, we hypothesized that the AP is a key site for peripheral GLP-1 to activate central autonomic regulatory sites. In this study, we found that many tyrosine hydroxylase (TH)-containing neurons in the AP expressed GLP-1Rs and Fos-IR after intravenous GLP-1R agonists. Furthermore, intravenous but not intracerebroventricular GLP-1R agonists induced TH transcription in the AP in vivo. In addition, GLP-1R agonists directly activated TH transcription in an in vitro cell system. Finally, we found that GLP-1-responsive TH neurons in the AP innervate autonomic control sites, including the parabrachial nucleus, nucleus of solitary tract, and ventrolateral medulla. These findings suggest that catecholamine neurons in the AP link peripheral GLP-1 and central autonomic control sites that mediate the diverse neuroendocrine and autonomic actions of peripheral GLP-1.

Animals↗

Regulation of melanocortin-4 receptor signaling: agonist-mediated desensitization and internalization.

Disruption of the hypothalamic melanocortin-4 receptor (MC4R) pathway results in obesity both in humans and rodents, demonstrating a crucial role for hypothalamic MC4Rs in the regulation of energy homeostasis. Because even haploinsufficiency of the MC4R gene can cause obesity in humans and mice, subtle changes in receptor numbers or signaling are likely to impact upon the regulation of food intake and energy expenditure. Little is known about the intracellular regulation of MC4R signaling. Using GT1-7 cells, we show for the first time that the MC4R undergoes ligand-mediated desensitization. We then addressed the possible mechanisms underlying the desensitization using HEK293 and COS-1 cells transfected with hemagglutinin-tagged human MC4R. Preexposure of GT1-7 cells that express endogenous MC4R to the agonist for MC4R, alpha-melanocyte-stimulating hormone, resulted in impaired cAMP formation to a second challenge of alpha-melanocyte-stimulating hormone. The desensitization of MC4R was accompanied by time-dependent internalization of the receptor in HEK293 cells, which was partly inhibited by pretreatment with a specific protein kinase A (PKA) inhibitor, H89. In COS-1 cells, overexpression of dominant-negative G protein-coupled receptor kinase (GRK) 2-K220R partly inhibited the agonist-mediated internalization of MC4R, whereas it did not in HEK293 cells. Overexpression of dominant-negative mutants of beta-arrestin1-V53D and dynamin I-K44A prevented agonist-mediated internalization of MC4R. Mutagenesis studies revealed that Thr312 and Ser329/330 in the C-terminal tail are potential sites for PKA and GRK phosphorylation and may play an essential role in the recruitment of beta-arrestin to the activated receptor. Our data demonstrate that, through PKA-, GRK-, beta-arrestin-, and dynamin-dependent processes, MC4R undergoes internalization in response to agonist, thereby providing novel insights into the regulation of MC4R signaling.

Agouti-Related Protein↗